We are interested in the genetic control of telomere structure and identity, and have focused on the model organism, Drosophila. Mutations in this organism are known that drastically increase or decrease the frequency of additions of telomere-specific retrotransposon to a chromosome end, suggesting that this process is under genetic control. We have identified one gene, Telomere elongation, which has mutations that increase the frequencies of both terminal gene conversion and targeted transposition, and are using positional information to clone the gene. The Tel gene maps to the middle of right arm of chromosome 3 to a region of approximately 320 kb, which includes 27 genes. Sequencing the coding regions of these genes did not identify a high probability candidate gene. The observations that the Tel mutations are genetically dominant and that deletions for the region do not have a telomere elongation phenotype suggest that the mutations are gain-of-function mutations and may be in controlling regions. Chromatin structure may regulate telomere length by controlling transcription of the telomeric retrotransposons and by controlling accessibility of the retroelements to the chromosome end. We have initiated a project to ask whether the telomere cap, which marks a chromosome end as distinct from a DNA double strand break, influences transposition of telomere specific retrotransposons to the chromosome end by asking whether mutations that modify the chromosome cap also influence the frequency of transposition. Currently, stocks are being constructed that will be used in this assay. These mutant stocks have mutations that increase the levels of telomeric retrotransposon transcripts and other mutations that disrupt the telomere cap. As mutations that disrupt the chromosome caps are homozygous lethal, these will be tested as heterozygotes. There is genetic evidence that the distinct chromatin structures associated with the terminal retrotransposon array and the telomere associated sequence within a single telomere blend together at the junction. We are trying to establish the technique of immunofluorescence-fluorescence in situ hybridization (IF-FISH) in the lab in order to identify chromatin structural proteins in specific telomere regions and ask whether changes in these regions affect telomere maintenance.